Opioid analgesics are one of the most commonly prescribed medication classes in the United States. Although these medications have been available for medical use for decades, their safety and effectiveness remain unclear. Available data from clinical trials are limited to highly selected patients and short term efficacy outcomes. Of great concern, information on the safety profile of these medications is even more scant. Several lines of in vivo experimental evidence indicate that opioid analgesics have significant immunosuppressive properties and could render opioid users susceptible to serious, potentially life-threatening infections. The immunosuppressive effects of opioid analgesics could be particularly troublesome for the elderly, who are commonly affected by persistent pain and are already at increased risk for infections. Given concerns about the safety of alternate analgesics (e.g. NSAIDs and COX-2 inhibitors), and the increasing widespread use of opioids, the determination and quantification of this potential risk is of great public health interest. Furthermore, there are a number of opioid analgesics currently available, but not all are expected to have the same immunosuppressive properties. Identifying those opioids with the lowest propensity to facilitate serious infections will be crucial to inform the selection of analgesics for the elderly. We propose to conduct a retrospective study of elderly persons enrolled in TennCare (Tennessee Medicaid) with the following specific aims: 1) To test the hypothesis that use of opioid analgesics increases the risk of serious infections; and, 2) To test the hypothesis that there is variation of the risk of serious infections for individual opioids. Th proposed studies will use a self-controlled case-series design, in which cases serve as their own controls, cancelling out the effects of fixed measured and unmeasured confounders, allowing control of relevant time-varying covariates; and, thus, allowing an unbiased estimation of the relative risk. PUBLIC HEALTH RELEVANCE: There is a long-standing concern that opioids can modify the immune system response and increase the risk of infections. These concerns are particularly relevant for elderly persons, who are commonly affected by pain and at increased risk for infections. Given the widespread use of opioid analgesics, the determination and quantification of this potential risk is of great public health interest. Moreover, identifying those opioids withthe lowest propensity to facilitate infections will be crucial to inform the selection of analgesics fo elderly patients.